A Upf3b-mutant mouse model with behavioral and neurogenesis defects.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). Here, we report the generation and characterization of mice harboring a null Upf3b allele. These Upf3b-null mice exhibit deficits in fear-conditioned learning, but not spatial learning. Upf3b-null mice also have a profound defect in prepulse inhibition (PPI), a measure of sensorimotor gating commonly deficient in individuals with SCZ and other brain disorders. Consistent with both their PPI and learning defects, cortical pyramidal neurons from Upf3b-null mice display deficient dendritic spine maturation in vivo. In addition, neural stem cells from Upf3b-null mice have impaired ability to undergo differentiation and require prolonged culture to give rise to functional neurons with electrical activity. RNA sequencing (RNAseq) analysis of the frontal cortex identified UPF3B-regulated RNAs, including direct NMD target transcripts encoding proteins with known functions in neural differentiation, maturation and disease. We suggest Upf3b-null mice serve as a novel model system to decipher cellular and molecular defects underlying ID and neurodevelopmental disorders.

Relating surface roughness and magnetic domain structure to giant magneto-impedance of Co-rich melt-extracted microwires.

Understanding the relationship between the surface conditions and giant magneto-impedance (GMI) in Co-rich melt-extracted microwires is key to optimizing their magnetic responses for magnetic sensor applications. The surface magnetic domain structure (SMDS) parameters of ~45 µm diameter Co69.25Fe4.25Si13B13.5-xZrx (x = 0, 1, 2, 3) microwires, including the magnetic domain period (d) and surface roughness (Rq) as extracted from the magnetic force microscopy (MFM) images, have been correlated with GMI in the range 1-1000 MHz. It was found that substitution of B with 1 at. % Zr increased d of the base alloy from 729 to 740 nm while retaining Rq from ~1 nm to ~3 nm. A tremendous impact on the GMI ratio was found, increasing the ratio from ~360% to ~490% at an operating frequency of 40 MHz. Further substitution with Zr decreased the high frequency GMI ratio, which can be understood by the significant increase in surface roughness evident by force microscopy. This study demonstrates the application of the domain period and surface roughness found by force microscopy to the interpretation of the GMI in Co-rich microwires.

Ferromagnetic glass-coated microwires with good heating properties for magnetic hyperthermia.

The heating properties of Fe71.7Si11B13.4Nb3Ni0.9 amorphous glass-coated microwires are explored for prospective applications in magnetic hyperthermia. We show that a single 5 mm long wire is able to produce a sufficient amount of heat, with the specific loss power (SLP) reaching a value as high as 521 W/g for an AC field of 700 Oe and a frequency of 310 kHz. The large SLP is attributed to the rectangular hysteresis loop resulting from a peculiar domain structure of the microwire. For an array of parallel microwires, we have observed an SLP improvement by one order of magnitude; 950 W/g for an AC field of 700 Oe. The magnetostatic interaction strength essential in the array of wires can be manipulated by varying the distance between the wires, showing a decreasing trend in SLP with increasing wire separation. The largest SLP is obtained when the wires are aligned along the direction of the AC field. The origin of the large SLP and relevant heating mechanisms are discussed.

Boosted Hyperthermia Therapy by Combined AC Magnetic and Photothermal Exposures in Ag/Fe3O4 Nanoflowers.

Over the past two decades, magnetic hyperthermia and photothermal therapy are becoming very promising supplementary techniques to well-established cancer treatments such as radiotherapy and chemotherapy. These techniques have dramatically improved their ability to perform controlled treatments, relying on the procedure of delivering nanoscale objects into targeted tumor tissues, which can release therapeutic killing doses of heat either upon AC magnetic field exposure or laser irradiation. Although an intense research effort has been made in recent years to study, separately, magnetic hyperthermia using iron oxide nanoparticles and photothermal therapy based on gold or silver plasmonic nanostructures, the full potential of combining both techniques has not yet been systematically explored. Here we present a proof-of-principle experiment showing that designing multifunctional silver/magnetite (Ag/Fe3O4) nanoflowers acting as dual hyperthermia agents is an efficient route for enhancing their heating ability or specific absorption rate (SAR). Interestingly, the SAR of the nanoflowers is increased by at least 1 order of magnitude under the application of both an external magnetic field of 200 Oe and simultaneous laser irradiation. Furthermore, our results show that the synergistic exploitation of the magnetic and photothermal properties of the nanoflowers reduces the magnetic field and laser intensities that would be required in the case that both external stimuli were applied separately. This constitutes a key step toward optimizing the hyperthermia therapy through a combined multifunctional magnetic and photothermal treatment and improving our understanding of the therapeutic process to specific applications that will entail coordinated efforts in physics, engineering, biology, and medicine.

From core/shell to hollow Fe/γ-Fe2O3 nanoparticles: evolution of the magnetic behavior.

High quality Fe/γ-Fe2O3 core/shell, core/void/shell, and hollow nanoparticles with two different sizes of 8 and 12 nm were synthesized, and the effect of morphology, surface and finite-size effects on their magnetic properties including the exchange bias (EB) effect were systematically investigated. We find a general trend for both systems that as the morphology changes from core/shell to core/void/shell, the magnetization of the system decays and inter-particle interactions become weaker, while the effective anisotropy and the EB effect increase. The changes are more drastic when the nanoparticles become completely hollow. Noticeably, the morphological change from core/shell to hollow increases the mean blocking temperature for the 12 nm particles but decreases for the 8 nm particles. The low-temperature magnetic behavior of the 12 nm particles changes from a collective super-spin-glass system mediated by dipolar interactions for the core/shell nanoparticles to a frustrated cluster glass-like state for the shell nanograins in the hollow morphology. On the other hand for the 8 nm nanoparticles core/shell and hollow particles the magnetic behavior is more similar, and a conventional spin glass-like transition is obtained at low temperatures. In the case of the hollow nanoparticles, the coupling between the inner and outer spin layers in the shell gives rise to an enhanced EB effect, which increases with increasing shell thickness. This indicates that the morphology of the shell plays a crucial role in this kind of exchange-biased systems.

Magnetocaloric effect and critical behavior in Pr0.5Sr0.5MnO3: an analysis of the validity of the Maxwell relation and the nature of the phase transitions.

The Maxwell relation, the Clausius-Clapeyron equation, and a non-iterative method to obtain the critical exponents have been used to characterize the magnetocaloric effect (MCE) and the nature of the phase transitions in Pr0.5Sr0.5MnO3, which undergoes a second-order paramagnetic to ferromagnetic (PM-FM) transition at TC ~ 247 K, and a first-order ferromagnetic to antiferromagnetic (FM-AFM) transition at TN ~ 165 K. We find that around the second-order PM-FM transition, the MCE (as represented by the magnetic entropy change, ΔSM) can be precisely determined from magnetization measurements using the Maxwell relation. However, around the first-order FM-AFM transition, values of ΔSM calculated with the Maxwell relation deviate significantly from those calculated by the Clausius-Clapeyron equation at the magnetic field and temperature ranges where a conversion between the AFM and FM phases occurs. A detailed analysis of the critical exponents of the second-order PM-FM transition allows us to correlate the short-range type magnetic interactions with the MCE. Using the Arrott-Noakes equation of state with the appropriate values of the critical exponents, the field- and temperature-dependent magnetization [Formula: see text] curves, and hence the [Formula: see text] curves, have been simulated and compared with experimental data. A good agreement between the experimental and simulated data has been found in the vicinity of the Curie temperature TC, but a noticeable discrepancy is present for [Formula: see text]. This discrepancy arises mainly from the coexistence of AFM and FM phases and the presence of ferromagnetic clusters in the AFM matrix.

Exchange bias effect in Au-Fe3O4 nanocomposites.

We report exchange bias (EB) effect in the Au-Fe3O4 composite nanoparticle system, where one or more Fe3O4 nanoparticles are attached to an Au seed particle forming 'dimer' and 'cluster' morphologies, with the clusters showing much stronger EB in comparison with the dimers. The EB effect develops due to the presence of stress at the Au-Fe3O4 interface which leads to the generation of highly disordered, anisotropic surface spins in the Fe3O4 particle. The EB effect is lost with the removal of the interfacial stress. Our atomistic Monte Carlo studies are in excellent agreement with the experimental results. These results show a new path towards tuning EB in nanostructures, namely controllably creating interfacial stress, and opens up the possibility of tuning the anisotropic properties of biocompatible nanoparticles via a controllable exchange coupling mechanism.

Evidence of a canted magnetic state in self-doped LaMnO(3+δ) (δ = 0.04): a magnetocaloric study.

We report a detailed investigation of the magnetocaloric properties of self-doped polycrystalline LaMnO(3+δ) with δ = 0.04. Due to the self-doping effect, the system exhibits a magnetic transition from a paramagnetic to ferromagnetic-like canted magnetic state (CMS) at ~120 K, which is associated with an appreciably large magnetocaloric effect (MCE). The CMS is an inhomogeneous magnetic phase developing due to a steady growth of antiferromagnetic correlation in its predominant ferromagnetic state below ∼120 K. The stabilization of CMS in this material is concluded from a comprehensive analysis of magnetocaloric data using Landau theory, which is in excellent agreement with our neutron diffraction study. The magnetic entropy change versus temperature curves for different applied fields collapse into a single curve, revealing a universal behavior of MCE. Our studies suggest that investigation of MCE is an effective technique to acquire fundamental understanding about the basic magnetic structure of a system with complex competing interactions.